Article type: Research Article
Authors: Hbibi, A. Tadlaouia | Lagorce, C.a; b | Wind, P.e | Spano, J.P.g | Des Guetz, G.a; c | Milano, G.h | Benamouzig, R.d | Rixe, O.g | Morere, J.-F.c | Breau, J.-L.c | Martin, A.a; b | Fagard, R.a; f; *
Affiliations: [a] Université Paris 13, EA 3406, Bobigny, France | [b] Service d'anatomopathologie, hôpital Avicenne, AP-HP, Bobigny, France | [c] Service d'oncologie médicale, hôpital Avicenne, AP-HP, Bobigny, France | [d] Service de gastro-entérologie, hôpital Avicenne, AP-HP, Bobigny, France | [e] Service de chirurgie digestive, hôpital Avicenne, AP-HP, Bobigny, France | [f] Service de biochimie, hôpital Avicenne, AP-HP, Bobigny, France | [g] Département d'oncologie médicale, GH Pitié – Salpêtrière, AP-HP, Paris, France | [h] Département d'oncopharmacologie, Centre Anti-Cancer Lacassagne, Nice, France
Correspondence:
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Corresponding author: Remi Fagard, Service de biochimie, hôpital Avicenne, 125 rue de Stalingrad, 93009 Bobigny Cedex, France. Tel.: +33 (0)1 48 95 59 28; Fax: +33 (0) 1 48 95 56 27; E-mail: [email protected].
Abstract: Aims:The Epidermal Growth Factor-Receptor (EGF-R) is frequently overexpressed in colorectal carcinoma (CRC) and patients can benefit from anti-EGF-R therapy. Yet, the relationship, within tumours, between EGF-R and the activity of downstream effectors such as the non-receptor tyrosine kinase p60c-src and the signal transducer and activator of transcription 3 (STAT3) has not been extensively analyzed. Methods and results:We evaluated EGF-R, tyrosine 416-phosphorylated p60c-src (P-p60c-src), STAT3 and tyrosine 705-phosphorylated STAT3 (P-STAT3) on Tissue Micro Array (TMA) from 126 patients with CRC. Composite immunohistochemistry scores based on the intensity of labelling and the percentage of positive cells were determined on TMA for EGF-R, P-p60c-src, STAT3 and P- STAT3. A high score was found in 56%, 61%, 62% and 27% of the cases for EGF-R, P-p60c-src, STAT3 and P-STAT3 respectively. There was a significant correlation between EGF-R and P-p60c-src (p=0.006) and between P-p60c-src and P-STAT3 (p=0.0009). STAT3 was significantly correlated with vascular emboli (p=0.03) and perineural invasion (p=0.02). Conclusions:The correlations between EGF-R, P-p60-src and P-STAT3 and some stage-related pathological features point to a critical role for a EGF-R-connected p60c-src-kinase-mediated pathway involving STAT3 and contributing to cell survival and proliferation within CRC tumours.
Keywords: Colorectal carcinoma, EGF-R, p60c-src, STAT3, tyrosine-phosphorylation
DOI: 10.3233/CBM-2008-4204
Journal: Cancer Biomarkers, vol. 4, no. 2, pp. 83-91, 2008
